TREM-1 promotes intestinal tumorigenesis.

Saurer, Leslie; Zysset, Daniel; Rihs, Silvia; Mager, Lukas; Gusberti, Matteo; Simillion, Cedric; Lugli, Alessandro; Zlobec, Inti; Krebs, Philippe; Müller, Christoph (2017). TREM-1 promotes intestinal tumorigenesis. Scientific Reports, 7(1), p. 14870. Nature Publishing Group 10.1038/s41598-017-14516-4

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Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune responses. Increasing evidence suggests a role for TREM-1 not only in acute pathogen-induced reactions but also in chronic and non-infectious inflammatory disorders, including various types of cancer. Here, we demonstrate that genetic deficiency in Trem1 protects from colorectal cancer. In particular, Trem1 (-/-) mice exhibited reduced tumor numbers and load in an experimental model of inflammation-driven tumorigenesis. Gene expression analysis of Trem1 (-/-) versus Trem1 (+/+) tumor tissue demonstrated distinct immune signatures. Whereas Trem1 (-/-) tumors showed an increased abundance of transcripts linked to adaptive immunity, Trem1 (+/+) tumors were characterized by overexpression of innate pro-inflammatory genes associated with tumorigenesis. Compared to adjacent tumor-free colonic mucosa, expression of Trem1 was increased in murine and human colorectal tumors. Unexpectedly, TREM-1 was not detected on tumor-associated Ly6C(-) MHC class II(+) macrophages. In contrast, TREM-1 was highly expressed by tumor-infiltrating neutrophils which represented the predominant myeloid population in Trem1 (+/+) but not in Trem1 (-/-) tumors. Collectively, our findings demonstrate a clear role of TREM-1 for intestinal tumorigenesis and indicate TREM-1-expressing neutrophils as critical players in colorectal tumor development.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Faculty Institutions > Teaching Staff, Faculty of Medicine

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Saurer, Leslie; Zysset, Daniel; Rihs, Silvia; Mager, Lukas; Zlobec, Inti; Krebs, Philippe and Müller, Christoph

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Christoph Müller

Date Deposited:

16 Nov 2017 07:53

Last Modified:

22 Oct 2019 22:23

Publisher DOI:

10.1038/s41598-017-14516-4

PubMed ID:

29093489

BORIS DOI:

10.7892/boris.106850

URI:

https://boris.unibe.ch/id/eprint/106850

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